AIDSTruth.org - New research

New research finds no evidence of increased risk of all-cause and non-AIDS death with long-term ARV use

Eduard Grebe — Wed, 18 Jan 2012 09:56:47 +0000

An important study has been published in AIDS that provides further evidence debunking one of the main claims of AIDS denialists, namely that ARVs do more harm than good (or even cause AIDS).

AIDS. 2012 Jan 28;26(3):315-323.

Long-term exposure to combination antiretroviral therapy and risk of death from specific causes: no evidence for any previously unidentified increased risk due to antiretroviral therapy.

Kowalska JD, Reekie J, Mocroft A, Reiss P, Ledergerber B, Gatell J, d'Arminio Monforte A, Phillips A, Lundgren JD, Kirk O; for the EuroSIDA study group.

Abstract

BACKGROUND:
Despite the known substantial benefits of combination antiretroviral therapy (cART), cumulative adverse effects could still limit the overall long-term treatment benefit. Therefore we investigated changes in the rate of death with increasing exposure to cART.

METHODS:
A total of 12 069 patients were followed from baseline, which was defined as the time of starting cART or enrolment into EuroSIDA whichever occurred later, until death or 6 months after last follow-up visit. Incidence rates of death were calculated per 1000 person-years of follow-up (PYFU) and stratified by time of exposure to cART (≥3 antiretrovirals): less than 2, 2-3.99, 4-5.99, 6-7.99 and more than 8 years. Duration of cART exposure was the cumulative time actually receiving cART. Poisson regression models were fitted for each cause of death separately.

RESULTS:
A total of 1297 patients died during 70 613 PYFU [incidence rate 18.3 per 1000 PYFU, 95% confidence interval (CI) 17.4-19.4], 413 due to AIDS (5.85, 95% CI 5.28-6.41) and 884 due to non-AIDS-related cause (12.5, 95% CI 11.7-13.3). After adjustment for confounding variables, including baseline CD4 cell count and HIV RNA, there was a significant decrease in the rate of all-cause and AIDS-related death between 2 and 3.99 years and longer exposure time. In the first 2 years on cART the risk of non-AIDS death was significantly lower, but no significant difference in the rate of non-AIDS-related deaths between 2 and 3.99 years and longer exposure to cART was observed.

CONCLUSION:
In conclusion, we found no evidence of an increased risk of both all-cause and non-AIDS-related deaths with long-term cumulative cART exposure.

PMID: 22112597

South African study provides additional evidence that AIDS conspiracy theories are associated with risky sex

Eduard Grebe — Mon, 27 Jun 2011 19:13:03 +0000

A study by two AIDSTruth contributors, Nicoli Nattrass and Eduard Grebe, has shown that belief in AIDS origin conspiracy theories like those promoted by AIDS denialists are associated with lower rates of condom usage among young adults. In addition, the study showed that young adults who trusted the denialist South African health minister (Manto Tshabalala-Msimang) more than her non-denialist successor were substantially more likely to believe conspiracy theories, while those who were not familiar with the denialiam-fighting activist group the Treatment Action Campaign were more likely to believe conspiracy theories and less likely to use a condom than those who were. This study adds to the evidence that state-supported denialism likely resulted (and continue to result) in unnecessary HIV infections in South Africa. Readers without subscriptions can access a preprint of the article. AIDS Behav. 2011 May 3. [Epub ahead of print]

AIDS Conspiracy Beliefs and Unsafe Sex in Cape Town

Grebe E, Nattrass N.

Abstract

This paper uses multivariate logistic regressions to explore: (1) potential socio-economic, cultural, psychological and political determinants of AIDS conspiracy beliefs among young adults in Cape Town; and (2) whether these beliefs matter for unsafe sex. Membership of a religious organisation reduced the odds of believing AIDS origin conspiracy theories by more than a third, whereas serious psychological distress more than doubled it and belief in witchcraft tripled the odds among Africans. Political factors mattered, but in ways that differed by gender. Tertiary education and relatively high household income reduced the odds of believing AIDS conspiracies for African women (but not men) and trust in President Mbeki's health minister (relative to her successor) increased the odds sevenfold for African men (but not women). Never having heard of the Treatment Action Campaign (TAC), the pro-science activist group that opposed Mbeki on AIDS, tripled the odds of believing AIDS conspiracies for African women (but not men). Controlling for demographic, attitudinal and relationship variables, the odds of using a condom were halved amongst female African AIDS conspiracy believers, whereas for African men, never having heard of TAC and holding AIDS denialist beliefs were the key determinants of unsafe sex. PMID: 21538083

Mortality by baseline CD4 cell count among HIV patients initiating antiretroviral therapy: evidence from a large cohort in Uganda

Eduard Grebe — Mon, 14 Mar 2011 21:57:09 +0000

Mills EJ, Bakanda C, Birungi J, Mwesigwa R, Chan K, Ford N, Hogg RS, Cooper C.

aFaculty of Health Sciences, University of Ottawa, Ottawa, Canada bThe AIDS Support Organization (TASO), Headquarters, Kampala, Uganda cBritish Columbia Centre for Excellence in HIV/AIDS, Vancouver, Canada dMédecins Sans Frontiers (MSF), Geneva, Switzerland eDivision of Infectious Diseases, The Ottawa Hospital, Ottawa, Canada.
Abstract
OBJECTIVE: Evaluations of CD4 cell count and other prognostic factors on the survival of HIV patients in sub-Saharan are extremely limited. Funders have been reticent to recommend earlier initiation of treatment. We aimed to examine the effect of baseline CD4 cell count on mortality using data from HIV patients receiving combination antiretroviral therapy (cART) in Uganda.
DESIGN: Observational study of patients age ≥14 years) enrolled in 10 clinics across Uganda for which TASO has data.
METHODS: CD4 cell count was stratified into categories (<50, 50-99, 100-149, 150-199, 200-249, 250-299, ≥300 cells/mm) and Cox proportional hazards regression was used to model the associations between CD4 cell count and mortality.
RESULTS: 22 315 patients were included. 1498 patients died during follow-up (6.7%) and 1433 (6.4%) of patients were lost to follow-up. Crude mortality rates (CMR) ranged from 53.8 per 1000 patient years (95% Confidence Interval [CI], 48.8-58.8) among those with CD4 cell counts of <50, to 15.7, (95% CI, 12.1-19.3) among those with ≥300 cells/mm. Relative to a baseline CD4 cell count of <50 cells/mm, the risk of mortality was 0.75 (95% CI, 0.65-0.88), 0.60 (95% CI, 0.51-0.70), 0.43 (0.37-0.50), and 0.41 (0.33-0.51) for those with baseline CD4 cell counts of 50-99, 100-149, 150-249, and ≥250 cells/mm, respectively.
CONCLUSION: Earlier initiation of cART is associated with increased survival benefits over deferred treatment.

PMID: 21330903 [PubMed - as supplied by publisher]

New research provides further clues about long-term non-progressors

Eduard Grebe — Sun, 12 Dec 2010 18:59:20 +0000

Denialists frequently cite the well-known phenomenon of some individuals with HIV living healthily for long periods without treatment as evidence that HIV does not cause AIDS. However, the existence of these rare individuals do not in fact disprove the science on HIV/AIDS. We debunked that myth here. Also, despite denialist claims to the contrary, research on how these individuals' immune systems control HIV for longer than usual has in fact been a priority and several studies have shed light on the mechanisms involved. A new study has now found slight differences in five amino acids in the HLA-B protein between long-term non-progressors and people who do not control HIV for longer than normal.

You can read a Reuters report on the study here.

Haiti study shows treating at CD4 of 350 versus 200 saves lives and reduces TB

Eduard Grebe — Sat, 17 Jul 2010 14:10:55 +0000

New England Journal of Medicine 363(3) July 15, 2010

Early versus Standard Antiretroviral Therapy for HIV-Infected Adults in Haiti

Patrice Severe et al.

Background

For adults with human immunodeficiency virus (HIV) infection who have CD4+ T-cell counts that are greater than 200 and less than 350 per cubic millimeter and who live in areas with limited resources, the optimal time to initiate antiretroviral therapy remains uncertain.

Methods

We conducted a randomized, open-label trial of early initiation of antiretroviral therapy, as compared with the standard timing for initiation of therapy, among HIV-infected adults in Haiti who had a confirmed CD4+ T-cell count that was greater than 200 and less than 350 per cubic millimeter at baseline and no history of an acquired immunodeficiency syndrome (AIDS) illness. The primary study end point was survival. The early-treatment group began taking zidovudine, lamivudine, and efavirenz therapy within 2 weeks after enrollment. The standard-treatment group started the same regimen of antiretroviral therapy when their CD4+ T-cell count fell to 200 per cubic millimeter or less or when clinical AIDS developed. Participants in both groups underwent monthly follow-up assessments and received isoniazid and trimethoprim–sulfamethoxazole prophylaxis with nutritional support.

Results

Between 2005 and 2008, a total of 816 participants — 408 per group — were enrolled and were followed for a median of 21 months. The CD4+ T-cell count at enrollment was approximately 280 per cubic millimeter in both groups. There were 23 deaths in the standard-treatment group, as compared with 6 in the early-treatment group (hazard ratio with standard treatment, 4.0; 95% confidence interval [CI], 1.6 to 9.8; P = 0.001). There were 36 incident cases of tuberculosis in the standard-treatment group, as compared with 18 in the early-treatment group (hazard ratio, 2.0; 95% CI, 1.2 to 3.6; P = 0.01).

Conclusions

Early initiation of antiretroviral therapy decreased the rates of death and incident tuberculosis. Access to antiretroviral therapy should be expanded to include all HIV-infected adults who have CD4+ T-cell counts of less than 350 per cubic millimeter, including those who live in areas with limited resources. (ClinicalTrials.gov number, NCT00120510.)

New research on elite controllers

Eduard Grebe — Wed, 28 Apr 2010 17:30:16 +0000

AIDS:15 May 2010 - Volume 24 - Issue 8 - p 1095–1105; doi: 10.1097/QAD.0b013e3283377a1e

HIV+ elite controllers have low HIV-specific T-cell activation yet maintain strong, polyfunctional T-cell responses

Owen, Rachel E; Heitman, John W; Hirschkorn, Dale F; Lanteri, Marion C; Biswas, Hope H; Martin, Jeffrey N; Krone, Melissa R; Deeks, Steven G; Norris, Philip J; the NIAID Center for HIV/AIDS Vaccine Immunology

Abstract

Objective: HIV+ elite controllers are a unique group of rare individuals who maintain undetectable viral loads in the absence of antiretroviral therapy. We studied immune responses in these individuals to inform vaccine development, with the goal of identifying the immune correlates of protection from HIV.

Methods: We compared markers of cellular activation, HIV-specific immune responses and regulatory T (Treg) cell frequencies in four groups of individuals: HIV-negative healthy controls, elite controllers (HIV RNA level <75 copies/ml), individuals on HAART and individuals with HIV RNA level more than 10 000 copies/ml (noncontrollers).

Results: Elite controllers possessed significantly lower levels of activated HIV-specific CD8+ T cells and of recently divided HIV-specific CD4+ T cells than noncontrollers, whereas these differences were not seen in the respective cytomegalovirus-specific T-cell populations. Elite controllers also mounted a stronger and broader cytokine and chemokine response following HIV-specific stimulation than individuals on HAART and noncontrollers. Finally, we found that HAART-suppressed individuals had elevated Treg cell frequencies, whereas elite controllers and noncontrollers maintained normal percentages of Treg cells.

Conclusion: Elite controllers maintain high levels of HIV-specific immune responses with low levels of HIV-specific T-cell activation and do not have elevated Treg cell levels. Based on these data an ideal HIV vaccine would induce strong HIV-specific immune responses whereas minimizing HIV-specific T-cell activation.

Read the article at AIDS.

Research shows pregress in maternal mortality but substantial impact of HIV

Eduard Grebe — Tue, 13 Apr 2010 15:15:18 +0000

The Lancet, Early Online Publication, 12 April 2010

doi:10.1016/S0140-6736(10)60518-1

Maternal mortality for 181 countries, 1980—2008: a systematic analysis of progress towards Millennium Development Goal 5

Margaret C Hogan MSc , Kyle J Foreman AB, Mohsen Naghavi MD, Stephanie Y Ahn BA, Mengru Wang BA, Susanna M Makela BS, Prof Alan D Lopez PhD, Prof Rafael Lozano MD, Prof Christopher JL Murray MD

Summary

Background

Maternal mortality remains a major challenge to health systems worldwide. Reliable information about the rates and trends in maternal mortality is essential for resource mobilisation, and for planning and assessment of progress towards Millennium Development Goal 5 (MDG 5), the target for which is a 75% reduction in the maternal mortality ratio (MMR) from 1990 to 2015. We assessed levels and trends in maternal mortality for 181 countries.

Methods

We constructed a database of 2651 observations of maternal mortality for 181 countries for 1980—2008, from vital registration data, censuses, surveys, and verbal autopsy studies. We used robust analytical methods to generate estimates of maternal deaths and the MMR for each year between 1980 and 2008. We explored the sensitivity of our data to model specification and show the out-of-sample predictive validity of our methods.

Findings

We estimated that there were 342 900 (uncertainty interval 302 100—394 300) maternal deaths worldwide in 2008, down from 526 300 (446 400—629 600) in 1980. The global MMR decreased from 422 (358—505) in 1980 to 320 (272—388) in 1990, and was 251 (221—289) per 100 000 livebirths in 2008. The yearly rate of decline of the global MMR since 1990 was 1·3% (1·0—1·5). During 1990—2008, rates of yearly decline in the MMR varied between countries, from 8·8% (8·7—14·1) in the Maldives to an increase of 5·5% (5·2—5·6) in Zimbabwe. More than 50% of all maternal deaths were in only six countries in 2008 (India, Nigeria, Pakistan, Afghanistan, Ethiopia, and the Democratic Republic of the Congo). In the absence of HIV, there would have been 281 500 (243 900—327 900) maternal deaths worldwide in 2008.

Interpretation

Substantial, albeit varied, progress has been made towards MDG 5. Although only 23 countries are on track to achieve a 75% decrease in MMR by 2015, countries such as Egypt, China, Ecuador, and Bolivia have been achieving accelerated progress.

Funding

Bill & Melinda Gates Foundation.

Read the article at The Lancet.

DART results show majority of HAART benefits can be achieved even without routine laboratory monitoring

Eduard Grebe — Wed, 13 Jan 2010 22:07:25 +0000

The results from the DART trial, reported this week in The Lancet, provide important evidence for HAART programmes in resource-constrained settings. From commentary by Phillips & Oosterhout published alongside the results:

In much of sub-Saharan Africa, the scale-up of use of antiretroviral therapy has been so far achieved without routine laboratory monitoring of drug toxicity and efficacy. Until now, there has not been substantive evidence about the consequences of delivering antiretrovirals without such routine monitoring.

In The Lancet today, the DART Trial Team present the Development of AntiRetroviral Therapy in Africa (DART) trial. In DART at enrolment, all participants started triple-drug antiretroviral therapy and were randomised to clinically driven monitoring versus laboratory plus clinical monitoring for toxicity (haematology and biochemistry) and efficacy (CD4-cell counts). Over 5 years, the proportions who had one or more serious adverse events were almost identical, while there was a somewhat higher proportion in the group on clinically driven monitoring who had disease progression or death (28%, compared with 21% in the other group; hazard ratio 1·31, 95% CI 1·14—1·51). This benefit of laboratory plus clinical monitoring is probably due to the use of CD4 count rather than presence of clinical symptoms alone to decide on when to switch to a second-line regimen. This criterion for switching on the basis of CD4 count is just one of the CD4-count switch criteria recommended by WHO; the other criteria (on the basis of CD4-count change from baseline and from peak) are problematic to implement without a baseline CD4 count and frequent CD4 counts being available thereafter.

The other particularly striking result from DART is the 5-year survival in both groups: 87% for clinical monitoring and 90% for laboratory plus clinical monitoring. Such rates of survival are for people in whom the initial median CD4-cell count was 86 cells per μL. For comparison, the survival in the Entebbe cohort of untreated HIV-positive people in 5 years was below 10% (data presented in the DART report), which emphasises the huge clinical benefits of antiretroviral therapy. The DART Trial Team concluded from their results that antiretroviral therapy can be delivered safely with good-quality clinical care, which would allow treatment delivery to be decentralised, and that there is a role for CD4 testing from the second year on antiretrovirals to guide the switch to second-line therapy, which should encourage accelerated development of simpler and cheaper point-of-care CD4 tests. The DART investigators should be complimented for exceptional achievement by completing this important trial with such a low loss to follow-up (7%) in challenging circumstances, which shows that excellent trials can be done in Africa.

The results from DART are very important for antiretroviral programmes, no matter what their current level of routine laboratory monitoring. Programmes that currently deliver antiretrovirals without any laboratory monitoring can be reassured that the vast majority (but not all) of the potential survival benefit of such therapy can be realised with the use of such a simple approach (albeit with particularly intensive and high-quality clinical monitoring, which is a substantial challenge to achieve in routine settings throughout sub-Saharan Africa). Similarly, no antiretroviral programme should enhance laboratory monitoring at the expense of putting more people in need on these drugs. Those clinics that do use routine measurement of biochemistry and haematology can reduce their laboratory costs to enable spending on other aspects of the programme (which has already started in some programmes). Programmes that monitor people on antiretrovirals with CD4 counts should consider adopting the switch criterion used in DART of CD4 count below 100 cells per μL (ie, only this one of the WHO-recommended criteria, rather than all three), and apply this criterion to people who have been on therapy for at least 2 years. Such a delay should help to reduce the number of people in whom a switch is made when viral load is actually suppressed.

Read the commentary at The Lancet (open access; registration required)

Details on the main paper below:

The Lancet, Volume 375, Issue 9709, Pages 123 - 131, 9 January 2010

Routine versus clinically driven laboratory monitoring of HIV antiretroviral therapy in Africa (DART): a randomised non-inferiority trial

DART Trial Team

Summary

Background

HIV antiretroviral therapy (ART) is often managed without routine laboratory monitoring in Africa; however, the effect of this approach is unknown. This trial investigated whether routine toxicity and efficacy monitoring of HIV-infected patients receiving ART had an important long-term effect on clinical outcomes in Africa.

Methods

In this open, non-inferiority trial in three centres in Uganda and one in Zimbabwe, 3321 symptomatic, ART-naive, HIV-infected adults with CD4 counts less than 200 cells per μL starting ART were randomly assigned to laboratory and clinical monitoring (LCM; n=1659) or clinically driven monitoring (CDM; n=1662) by a computer-generated list. Haematology, biochemistry, and CD4-cell counts were done every 12 weeks. In the LCM group, results were available to clinicians; in the CDM group, results (apart from CD4-cell count) could be requested if clinically indicated and grade 4 toxicities were available. Participants switched to second-line ART after new or recurrent WHO stage 4 events in both groups, or CD4 count less than 100 cells per μL (LCM only). Co-primary endpoints were new WHO stage 4 HIV events or death, and serious adverse events. Non-inferiority was defined as the upper 95% confidence limit for the hazard ratio (HR) for new WHO stage 4 events or death being no greater than 1·18. Analyses were by intention to treat. This study is registered, number ISRCTN13968779.

Findings

Two participants assigned to CDM and three to LCM were excluded from analyses. 5-year survival was 87% (95% CI 85—88) in the CDM group and 90% (88—91) in the LCM group, and 122 (7%) and 112 (7%) participants, respectively, were lost to follow-up over median 4·9 years' follow-up. 459 (28%) participants receiving CDM versus 356 (21%) LCM had a new WHO stage 4 event or died (6·94 [95% CI 6·33—7·60] vs 5·24 [4·72—5·81] per 100 person-years; absolute difference 1·70 per 100 person-years [0·87—2·54]; HR 1·31 [1·14—1·51]; p=0·0001). Differences in disease progression occurred from the third year on ART, whereas higher rates of switch to second-line treatment occurred in LCM from the second year. 283 (17%) participants receiving CDM versus 260 (16%) LCM had a new serious adverse event (HR 1·12 [0·94—1·32]; p=0·19), with anaemia the most common (76 vs 61 cases).

Interpretation

ART can be delivered safely without routine laboratory monitoring for toxic effects, but differences in disease progression suggest a role for monitoring of CD4-cell count from the second year of ART to guide the switch to second-line treatment.

Funding

UK Medical Research Council, the UK Department for International Development, the Rockefeller Foundation, GlaxoSmithKline, Gilead Sciences, Boehringer-Ingelheim, and Abbott Laboratories.

Read the paper at The Lancet (open access; registration required)

Chigwedere & Essex refute AIDS denialist arguments in AIDS & Behavior

Eduard Grebe — Tue, 12 Jan 2010 22:46:18 +0000

Also see the comment piece Still Crazy After All These Years (open access) by Nicoli Nattrass that appears in the same issue of AIDS & Behavior.

Update (22/01/2010): See AIDS Denialism Under Fire From Researchers by Nora Proops in The AIDS Beacon.

AIDS & Behavior. 2010 Jan 8. [Epub ahead of print]

AIDS Denialism and Public Health Practice

Chigwedere P, Essex M.

In this paper, we respond to AIDS denialist arguments that HIV does not cause AIDS, that antiretroviral drugs are not useful, and that there is no evidence of large-scale deaths from AIDS, and discuss the key implications of the relationship between AIDS denialism and public health practice. We provide a brief history of how the cause of AIDS was investigated, of how HIV fulfills Koch's postulates and Sir Bradford Hill's criteria for causation, and of the inconsistencies in alternatives offered by denialists. We highlight clinical trials as the standard for assessing efficacy of drugs, rather than anecdotal cases or discussions of mechanism of action, and show the unanimous data demonstrating antiretroviral drug efficacy. We then show how statistics on mortality and indices such as crude death rate, life expectancy, child mortality, and population growth are consistent with the high mortality from AIDS, and expose the weakness of statistics from death notification, quoted by denialists. Last we emphasize that when denialism influences public health practice as in South Africa, the consequences are disastrous. We argue for accountability for the loss of hundreds of thousands of lives, the need to reform public health practice to include standards and accountability, and the particular need for honesty and peer review in situations that impact public health policy.

PMID: 20058063

Read the full article on SpringerLink (open access)

doi:10.1007/s10461-009-9654-7

Declines in Mortality Rates and Changes in Causes of Death in HIV-1-Infected Children During the HAART Era

Eduard Grebe — Tue, 29 Dec 2009 13:11:02 +0000

J Acquir Immune Defic Syndr. 2010 Jan;53(1):86-94.

Brady MT, Oleske JM, Williams PL, Elgie C, Mofenson LM, Dankner WM, Van Dyke RB; for the Pediatric AIDS Clinical Trials Group219/219C Team.

CONTEXT: Introduction of highly active antiretroviral therapy has significantly decreased mortality in HIV-1-infected adults and children. Although an increase in non-HIV-related mortality has been noted in adults, data in children are limited.

OBJECTIVES:: To evaluate changes in causes and risk factors for death among HIV-1-infected children in Pediatric AIDS Clinical Trials Group 219/219C.

DESIGN, SETTING, AND PARTICIPANTS:: Multicenter, prospective cohort study designed to evaluate long-term outcomes in HIV-1-exposed and infected US children. There were 3553 HIV-1-infected children enrolled and followed up between April 1993 and December 2006, with primary cause of mortality identified in the 298 observed deaths.

MAIN OUTCOME MEASURES:: Mortality rates per 100 child-years overall and by demographic factors; survival estimates by birth cohort; and hazard ratios for mortality by various demographic, health, and antiretroviral treatment factors were determined.

RESULTS:: Among 3553 HIV-1-infected children followed up for a median of 5.3 years, 298 deaths occurred. Death rates significantly decreased between 1994 and 2000, from 7.2 to 0.8 per 100 person-years, and remained relatively stable through 2006. After adjustment for other covariates, increased risk of death was identified for those with low CD4 and AIDS-defining illness at entry. Decreased risks of mortality were identified for later birth cohorts, and for time-dependent initiation of highly active antiretroviral therapy (hazard ratio 0.54, P < 0.001). The most common causes of death were "End-stage AIDS" (N = 48, 16%) and pneumonia (N = 41, 14%). The proportion of deaths due to opportunistic infections (OIs) declined from 37% in 1994-1996 to 24% after 2000. All OI mortality declined during the study period. However, a greater decline was noted for deaths due to Mycobacterium avium complex and cryptosporidium. Deaths from "End-stage AIDS," sepsis and renal failure increased.

CONCLUSIONS:: Overall death rates declined from 1993 to 2000 but have since stabilized at rates about 30 times higher than for the general US pediatric population. Deaths due to OIs have declined, but non-AIDS-defining infections and multiorgan failure remain major causes of mortality in HIV-1-infected children.

PMID: 20035164.

Read at JAIDS.

Science: HIV Natural Resistance Field Finally Overcomes Resistance

Eduard Grebe — Tue, 29 Dec 2009 12:58:18 +0000

Science 11 December 2009: Vol. 326. no. 5959, pp. 1476 - 1477

Dozens of studies have been examining people who fend off HIV despite repeated exposures in an effort to find genetic or immunologic factors that can help guide AIDS vaccine research. But all too often the leads point in contradictory directions, in part because investigators use different assays to probe their samples, and there is little coordination among them. Many labs also use wildly varying criteria to decide who qualifies as HIV-resistant, making it difficult to sort out which study subjects were truly exposed and uninfected, were exposed and have an occult infection, or were never exposed in the first place. At the first-ever meeting on natural immunity to HIV, held from 15 to 17 November, researchers attempted to hammer out these and other issues.

Read the article at Science.

doi: 10.1126/science.326.5959.1476

The effect of combined antiretroviral therapy on the overall mortality of HIV-infected individuals

Eduard Grebe — Sun, 20 Dec 2009 19:30:32 +0000

AIDS. 2010 Jan 2;24(1):123-37.

HIV-CAUSAL Collaboration.

OBJECTIVE: To estimate the effect of combined antiretroviral therapy (cART) on mortality among HIV-infected individuals after appropriate adjustment for time-varying confounding by indication. DESIGN: A collaboration of 12 prospective cohort studies from Europe and the United States (the HIV-CAUSAL Collaboration) that includes 62 760 HIV-infected, therapy-naive individuals followed for an average of 3.3 years. Inverse probability weighting of marginal structural models was used to adjust for measured confounding by indication. RESULTS: Two thousand and thirty-nine individuals died during the follow-up. The mortality hazard ratio was 0.48 (95% confidence interval 0.41-0.57) for cART initiation versus no initiation. In analyses stratified by CD4 cell count at baseline, the corresponding hazard ratios were 0.29 (0.22-0.37) for less than 100 cells/microl, 0.33 (0.25-0.44) for 100 to less than 200 cells/microl, 0.38 (0.28-0.52) for 200 to less than 350 cells/microl, 0.55 (0.41-0.74) for 350 to less than 500 cells/microl, and 0.77 (0.58-1.01) for 500 cells/microl or more. The estimated hazard ratio varied with years since initiation of cART from 0.57 (0.49-0.67) for less than 1 year since initiation to 0.21 (0.14-0.31) for 5 years or more (P value for trend <0.001). CONCLUSION: We estimated that cART halved the average mortality rate in HIV-infected individuals. The mortality reduction was greater in those with worse prognosis at the start of follow-up.

PMID: 19770621

Survival of Children with HIV in the United States Has Improved Dramatically Since 1990s, New Analysis Shows

Eduard Grebe — Sun, 20 Dec 2009 18:31:08 +0000

Mortality Rate Still Higher Than for Children without HIV

The death rates of children with HIV have decreased ninefold since doctors started prescribing cocktails of antiretroviral drugs in the mid-1990s, concludes a large-scale study of the long-term outcomes of children and adolescents with HIV in the United States. In spite of this improvement, however, young people with HIV continue to die at 30 times the rate of youth of similar age who do not have HIV, found researchers from the National Institutes of Health and other institutions.

Earlier studies have shown that adults with HIV are living longer because of improved multi-drug antiretroviral regimens known as highly active antiretroviral therapy (HAART). However, limited information has existed about the effectiveness of HAART in improving the survival of children with HIV. The current analysis, published in the Dec. 15 issue of the Journal of Acquired Immune Deficiency Syndromes, delineates the effects of HAART on the rates and causes of death for HIV-infected children and adolescents.

Conducted by the Pediatric AIDS Clinical Trials Group, the study was co-funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the National Institute of Allergy and Infectious Diseases (NIAID), both part of NIH. The study’s first author is Michael T. Brady, M.D., of Nationwide Children’s Hospital in Columbus, Ohio.

In 1994, the mortality rate for HIV-infected children and youth younger than 21 years of age in the United States was 7.2 deaths per 100 person years (a rate based on the number of children in the study and the total number of years each child was followed). By 2000, that rate had plummeted to 0.8 deaths per 100 person years and remained stable through 2006. The mean age at death for HIV-infected youth in the study more than doubled from 8.9 years in 1994 to 18.2 years in 2006.

Although this represents a dramatic improvement in survival, the death rate for children with HIV is approximately 30 times higher than that of similarly aged U.S. children who do not have HIV. Multi-organ failure and kidney disease are now major causes of death for HIV-infected children and adolescents. Infections also continue to cause deaths in this group of patients. However, the type of infections has changed, from infections traditionally associated with AIDS to infections that are more common in children without HIV infection.

"The findings are very encouraging, but they still show a need for improvement," said Alan Guttmacher, M.D., acting director of NICHD. "For both adults and children, combination antiretroviral therapy is highly effective in preventing the opportunistic infections and other complications resulting from HIV infection. We must now better understand and pursue treatments for children and adolescents to address the other conditions resulting from HIV infection."

"Basic research and clinical studies funded by NIH beginning in the 1980s laid the foundation for the development of the more than two dozen drugs now available to fight HIV, enabling many children infected with the virus to live into adulthood,"said NIAID Director Anthony S. Fauci, M.D. "Now we face the challenge of effectively treating the consequences of long-term HIV infection in people who have been infected since childhood."

Between 1993 and 2006, the researchers tracked 3,553 U.S. children and adolescents infected with HIV. Of those children, 298 died. Growing numbers of children with HIV began receiving HAART between 1994 and 2000, and death rates declined annually during that period. Nearly 60 percent of all deaths in the study occurred before 1997, before the advent of HAART for the treatment of children; moreover, children who died were almost four times as likely to have never received HAART as those who survived.

"A wonderful change has occurred: Most HIV-infected children now reach adulthood," said Lynne Mofenson, M.D., an author of the paper and chief of the Pediatric, Adolescent and Maternal AIDS branch at NICHD. "Will these children have a normal lifespan? Unfortunately, we don’t have all the answers yet. Currently, we don’t have the means to prevent all the complications of HIV infection."

In the early years of the study, secondary infections killed more than one-third of the children who died, but from 2002 to 2006, that proportion fell to less than one-fourth. Over time, children and adolescents with HIV became more likely to die of kidney failure, stroke, or AIDS-induced multiple organ failure.

To try to prevent these deaths, another long-term study of children with HIV called the Pediatric HIV/AIDS Cohort Study is being funded by NICHD, NIAID, the National Institute on Drug Abuse, the National Institute on Deafness and Other Communication Disorders, the National Heart, Lung, and Blood Institute, and the National Institute of Mental Health. This study is monitoring how children and adolescents with the virus grow and develop, what complications they experience, and whether they experience side effects from their medication.

"To keep these children healthy, we need to learn more about how HIV and anti-HIV drugs affect their growing bodies," said Dr. Mofenson. "We took a big leap in our understanding with this study, and the next pediatric cohort study will lead to even more improvements in understanding HIV infection and its treatment in youth."

In addition to Drs. Brady and Mofenson, the other authors of the article are James M. Oleske, M.D., M.P.H., of the University of Medicine and Dentistry of New Jersey; Paige L. Williams, Ph.D., of the Harvard School of Public Health; Carol Elgie of Frontier Science Technology and Research Foundation; Wayne M. Dankner, M.D., of Parexel International and Duke University Medical Center, and Russell B. Van Dyke, M.D., of Tulane University.

The NICHD sponsors research on development, before and after birth; maternal, child, and family health; reproductive biology and population issues; and medical rehabilitation. For more information, visit the Institute’s Web site at http://www.nichd.nih.gov/.

NIAID conducts and supports research—at NIH, throughout the United States, and worldwide—to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov.

The National Institutes of Health (NIH) — The Nation's Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

Six-month gain in weight, height, and CD4 predict subsequent antiretroviral treatment responses in HIV-infected South African children

Eduard Grebe — Sun, 20 Dec 2009 16:00:00 +0000

AIDS. 2010 Jan 2;24(1):139-46.

Yotebieng M, Van Rie A, Moultrie H, Meyers T.

OBJECTIVES: Construct percentile curves for 6-month gain in weight, height, CD4 cell count, and CD4 percentage (CD4%) in children initiating ART, and to assess the association between lower percentiles and subsequent ART responses. DESIGN: Cohort of 1394 HIV-infected children initiating ART between April 2004 and March 2008, Johannesburg, South Africa METHODS: The generalized additive model for location, scale, and shape was used to construct percentile curves for 6-month gain in weight, height, CD4 cell count, and CD4%. Cox proportional models were used to assess the association between lower percentiles of each distribution and death, virological suppression, and treatment failure between 6 to 36 months post-ART initiation. RESULTS: Lower percentiles for gain in weight, CD4, and CD4% count after 6 months of ART, but not height, were associated with poor subsequent treatment outcomes independent of baseline characteristics, with increasing strength of association as percentiles decreased. Age-specific 6-month post-ART weight gain in our cohort was substantially higher compared with 6-month weight gain in non-HIV-infected American children of the Fels Institute cohort and the attained weight-for-age at 6 months post-ART plotted on WHO weight-for-age growth charts were not associated with subsequent treatment outcomes. CONCLUSION: Gain in CD4% in the first 6 months of ART was the best predictor of poor subsequent ART outcomes. In areas with limited access to CD4%, weight gain post-ART using our newly developed reference distributions for HIV-infected children on ART is a good alternative to CD4%, and clearly superior to the commonly used 'Road-to-Health' weight-for-age charts.

PMID: 19940744

Conspiracy beliefs about HIV associated with lower adherence.

Eduard Grebe — Thu, 10 Dec 2009 19:03:22 +0000

A new study has found poorer adherence to antiretroviral therapy among African-American men with HIV who hold conspiracy beliefs, e.g. that HIV is a man-made virus designed to kill Africans.

JAIDS. 2009 Dec 09.

Conspiracy Beliefs About HIV Are Related to Antiretroviral Treatment Nonadherence Among African American Men With HIV

Bogart, Laura M PhD; Wagner, Glenn PhD; Galvan, Frank H PhD; Banks, Denedria MSW

Background: Medical mistrust is prevalent among African Americans and may influence health care behaviors such as treatment adherence. We examined whether a specific form of medical mistrust-HIV conspiracy beliefs (eg, HIV is genocide against African Americans)-was associated with antiretroviral treatment nonadherence among African American men with HIV.

Methods: On baseline surveys, 214 African American men with HIV reported their agreement with 9 conspiracy beliefs, sociodemographic characteristics, depression symptoms, substance use, disease characteristics, medical mistrust, and health care barriers. Antiretroviral medication adherence was monitored electronically for one month postbaseline among 177 men in the baseline sample.

Results: Confirmatory factor analysis revealed 2 distinct conspiracy belief subscales: genocidal beliefs (eg, HIV is manmade) and treatment-related beliefs (eg, people who take antiretroviral treatments are human guinea pigs for the government). Both subscales were related to nonadherence in bivariate tests. In a multivariate logistic regression, only treatment-related conspiracies were associated with a lower likelihood of optimal adherence at one-month follow-up (odds ratio = 0.60, 95% confidence interval = 0.37 to 0.96, P < 0.05).

Conclusions: HIV conspiracy beliefs, especially those related to treatment mistrust, can contribute to health disparities by discouraging appropriate treatment behavior. Adherence-promoting interventions targeting African Americans should openly address such beliefs.

doi: 10.1097/QAI.0b013e3181c57dbc

PMID: 19952767

ART halves overall mortality of HIV-infected individuals

Eduard Grebe — Tue, 08 Dec 2009 15:06:54 +0000

AIDS. 2010 Jan 2;24(1):123-37.

The effect of combined antiretroviral therapy on the overall mortality of HIV-infected individuals

The HIV-CAUSAL Collaboration

Abstract

Objective: To estimate the effect of combined antiretroviral therapy (cART) on mortality among HIV-infected individuals after appropriate adjustment for time-varying confounding by indication.

Design: A collaboration of 12 prospective cohort studies from Europe and the United States (the HIV-CAUSAL Collaboration) that includes 62 760 HIV-infected, therapy-naive individuals followed for an average of 3.3 years. Inverse probability weighting of marginal structural models was used to adjust for measured confounding by indication.

Results: Two thousand and thirty-nine individuals died during the follow-up. The mortality hazard ratio was 0.48 (95% confidence interval 0.41-0.57) for cART initiation versus no initiation. In analyses stratified by CD4 cell count at baseline, the corresponding hazard ratios were 0.29 (0.22-0.37) for less than 100 cells/μl, 0.33 (0.25-0.44) for 100 to less than 200 cells/μl, 0.38 (0.28-0.52) for 200 to less than 350 cells/μl, 0.55 (0.41-0.74) for 350 to less than 500 cells/μl, and 0.77 (0.58-1.01) for 500 cells/μl or more. The estimated hazard ratio varied with years since initiation of cART from 0.57 (0.49-0.67) for less than 1 year since initiation to 0.21 (0.14-0.31) for 5 years or more (P value for trend <0.001).

Conclusion: We estimated that cART halved the average mortality rate in HIV-infected individuals. The mortality reduction was greater in those with worse prognosis at the start of follow-up.

doi: 10.1097/QAD.0b013e3283324283

PMID: 19770621

Still Crazy After All These Years: The Challenge of AIDS Denialism for Science

Eduard Grebe — Mon, 07 Dec 2009 18:09:17 +0000

AIDSTruth contributor Nicoli Nattrass writes in AIDS and Behavior:

In his new book, Denying AIDS, Seth Kalichman observes that people are surprised by the persistence of AIDS denialists: “Are they still around?”[1, p. 1] he is often asked. And it is a good question. Given the large body of scientific and clinical evidence on HIV disease and treatment (expertly summarized by Chigwedere and Essex in this issue of AIDS and Behavior) it is indeed strange that Peter Duesberg and his followers still claim HIV is harmless and that antiretrovirals cause rather than treat AIDS. While such dissident views were intellectually respectable in the 1980s when HIV science was new, they make little sense today. Thus Joseph Sonnabend, a doctor who treated some of the earliest AIDS cases in New York and was well known for arguing that environmental factors may be more important than a virus in driving AIDS, was quick to change his mind once antiretroviral treatment was shown to act against HIV and transform the health of his patients [2, p. 25]. Peter Duesberg, by contrast, refused to accept the evidence, thereby earning the label ‘denialist’ rather than ‘dissident’ [1, 2].

Duesberg may be pathologically contrarian in this respect, but he has an enduring appeal. Kalichman [1] argues that this is in large part because his claim that HIV is harmless reinforces the normal process of denial most people undergo when faced with traumatizing information—such as a positive HIV test result. Another reason is that Duesberg’s views are promoted in books, on denialist websites and blogs and by a persistent trickle of ‘Duesberg-as-oppressed-hero-scientist’ stories from independent film-makers and journalists. It is precisely because he holds a post at Berkeley and is an elected member of the National Academy of Sciences, that Duesberg has been able to build the media profile that sustains him. As Epstein argues, by ‘using his scientific credentials to buy him popular support, then using the popular support to push for recognition by his colleagues—Duesberg gained staying power’ [3, p. 142].

This has resulted in HIV science being represented as fundamentally contested in ways which it actually is not. And because of the threat AIDS denialism poses both to public health and to the authority of HIV science itself, scientists have found it necessary, time and time again, to respond to Duesberg’s claims, despite their long having been demolished [see e.g. 4–8]. Chigwedere and Essex’s paper in this issue is one more such refutation in a long line of refutations. What makes their paper different is that in addition to marshalling the key evidence in support of the scientific consensus on HIV, they criticize Duesberg for inspiring South Africa’s ex-President Mbeki AIDS policies (thereby causing hundreds of thousands of unnecessary deaths) and they take him to task for suggesting (in a co-authored paper initially published in Medical Hypotheses but subsequently withdrawn by the publisher) that the African AIDS epidemic does not exist.

Chigwedere and Essex are clearly angry—the emotion is evident on every page. This is not merely because of the dangers Duesberg’s intransigence poses for public health but because of his refusal to change his views when the evidence demands it. This has long been a source of frustration for HIV scientists. For example, Robert Gallo, the co-discoverer of HIV, has described him as ‘like a little dog that won’t let go’ [in 6, p. 1644] and John Moore [9], an eminent virologist at Weill Cornell Medical School, has likened Duesberg to Monty Python’s black knight who keeps fighting despite having all of his limbs cut off by his opponent. And the problem is far more than intellectual because disregarding evidence not only undermines scientific progress, but it threatens the social basis which makes such progress possible. Respect for the evidence and for the people who generate it is a core value in the scientific community—and it is precisely this that Duesberg flouts. Warren Winkelstein, one of the early HIV epidemiologists, recalls how, at a meeting of the National Academy of Sciences in Washington to discuss Duesberg’s theories, Duesberg would frequently get up, wander around the room and start talking to reporters. In his view, Duesberg simply ‘wasn’t listening to what was being said’ [in 10, p. 131). The message Duesberg was broadcasting then, and in all his statements on AIDS, is loud and clear: he alone is correct and the work of others is not worth considering.

Read the full article on SpringerLink.

doi:10.1007/s10461-009-9641-z

Call for Mandatory Disclosure of Pharmaceutical Industry-Funded Events for Health Professionals

Eduard Grebe — Thu, 26 Nov 2009 13:52:56 +0000

We endorse this call for mandatory disclosure.

Mandatory Disclosure of Pharmaceutical Industry-Funded Events for Health Professionals

Robertson J, Moynihan R, Walkom E, Bero L, Henry D (2009) PLoS Med 6(11): e1000128. doi:10.1371/journal.pmed.1000128

Summary Points

There are moves internationally to ensure greater disclosure of gifts and educational events for doctors paid for by pharmaceutical manufacturers. However, there is no agreement on appropriate standards of disclosure. In Australia, since mid-2007, there has been mandatory reporting of details of every industry-sponsored event, including the costs of any hospitality provided.
Examination of the Australian data shows that although expenditure at individual events is often modest, cumulative expenditure is high, particularly in the case of medical specialists prescribing high cost drugs—oncologists, endocrinologists, and cardiologists.
Although a significant advance, the new Australian reporting standards do not allow assessment of the educational value of sponsored events, and do not include details of speakers or educational content for most events. However, doctors in training are often present at these events.
At present, the standards of disclosure are inadequate and should not be tied to an arbitrary monetary value of gifts or sponsorship. Reporting standards should require the names of the speakers presenting, whether sponsors played a role in suggestion or selection of speakers or the development of the content of presentations, and the nature of any direct or indirect financial ties between the speakers and the sponsors.

For boxes, tables and figures, visit the original article on Plos Medicine.

Background

We are in a period of unprecedented scrutiny of the relationships between the pharmaceutical industry and doctors [1]–[4]. Legislators are now considering how they might become involved in the regulation of these practices. This is a telling comment on the perceived failure of the medical profession to regulate itself and of self-regulation by industry. But reliable and comprehensive data on the nature and extent of industry sponsorship are rare. Several states in the US have mandatory disclosure laws for physician payments, but these data have proved difficult to access and analyse [5]. The US Congress is considering new mechanisms for revealing industry–professional interactions (the so-called “Sunshine” Acts) [6],[7].

One of the first countries to move towards greater transparency was Australia. The pharmaceutical industry representative body, Medicines Australia, has a self-regulatory Code of Conduct that sets standards for the ethical marketing and promotion of prescription pharmaceutical products for its member companies. In addition to monitoring of promotional activities, a Code of Conduct Committee adjudicates on complaints regarding pharmaceutical company activities [8]. In 2007, the Australian Competition Tribunal placed disclosure requirements on Medicines Australia. It approved that body's Code of Conduct for industry–professional relationships on the condition that details of every sponsored event, including the costs of any hospitality, were posted on their website [9],[10]. Reporting commenced in July 2007 and data are updated six monthly [8].

In this Policy Forum we examine the Australian data and argue that although a definite advance, the Australian disclosure requirements fall short of what is required. We propose more comprehensive reporting standards, which should have application to other settings and jurisdictions.

Australian Experience of Pharmaceutical Company Disclosures

In Australia, the emphasis in disclosure is on monitoring the level and type of sponsorship of educational events rather than documenting the dollar value of gifts and other payments to physicians. Since 2007 pharmaceutical companies have been required to report all functions (educational events) provided or sponsored for health professionals. They are required to disclose the following: the venue; the professional status of attendees; a description of the function and duration of the educational content of events; the nature of the hospitality; the total cost of hospitality; the numbers of attendees; and the total cost of the function [11].

The first report, covering the period July to December 2007, provided details of 14,649 events (Table 1) [12]. This total is equivalent to almost 600 events per week nationally, at a cost of around AUD$1 million/week (US$879,074.00). Put another way, the pharmaceutical industry spends, on average, around AUD$1,000 annually on each doctor through sponsorship of such events. The top five companies in terms of the numbers of sponsored events were Astra Zeneca, Pfizer, Sanofi Aventis, Janssen Cilag, and Eli Lilly (Table 1). The most generous of the active companies (those with >100 functions in 6 months) was Bristol Myers Squibb, with an average cost per head of AUD$95.26. In contrast, Alphapharm (a generics manufacturer) sponsored 441 events (mostly in professional rooms with a sandwich lunch) at an average cost per head of AUD$18.24 (Table 1).

Hospitality (food, beverages, travel, accommodation) accounted for around AUD$17 million of the total of AUD$31 million spent on functions. Thirty-five percent of sponsored events (n = 5,174) were held in restaurants, hotels, or function centres. The average cost per head was much higher when the venue was a restaurant (AUD$71.35) than in a hospital (AUD$12.11). In 7.2% of cases (n = 1,062) expenditure exceeded AUD$100 per head (examples are given in Box 1). There were 74 events (0.5%) with total outlays per head on hospitality in excess of AUD$500.

Medical specialists were present at 62% (n = 9,018) of events, family physicians at 30% (n = 4,437), nurses at 26% (n = 3,820), and pharmacists at less than 5% (n = 621) of events. Registrars (medical specialists in training) were present at 19% (n = 2,827) of events; in 179 instances they were the only attendees. The medical subspecialties most often featured were psychiatry (17.9%), and oncology (15.2%), who received industry hospitality roughly three times as often as any other subspeciality (Table 2). The largest per head expenditure was directed at endocrinologists, oncologists, and cardiologists (Table 2). Companies spent considerably more on restaurant meals for doctors (AUD$76.73) than for nurses (AUD$48.78).

Companies reported no responsibility for the educational content in only 9% of events (n = 1,287). Likewise, continuing medical education (CME)/continuing professional development (CPD) points were allocated to 9% of events (n = 1,270). Just over 20% of all events were described as “journal club” or “grand rounds” (n = 3,035), mostly conducted in hospitals. The majority of events (n = 10,723, 73.2%) were a mix of meetings of various kinds, including workshops and in-service training activities; only 4% (n = 591) were described as “conferences.” Table 3 shows the topics discussed, the most common being cardiology, diabetes, oncology, psychiatry, and respiratory medicine. The most common specific topics were hypertension, osteoporosis, breast cancer, type-2 diabetes, and depression. All represent large and important markets for pharmaceutical products. Topic descriptions, where provided, often matched the product portfolio of the sponsor, although there were few mentions of specific drug names (n = 582, 4%).

Importantly, Australian companies are not required to disclose the names of the speakers, whether sponsors played a role in their selection or in the choice of the content of presentations. They are also not required to disclose the nature of any financial ties between their companies and the speakers.

Why Do We Need Better Disclosure?

The information provided by Medicines Australia points to a high level of contact between pharmaceutical manufacturers and health professionals, particularly doctors. The per-person expenditure was greatest for medical specialists who prescribe high cost drugs—oncologists, endocrinologists, and cardiologists. Generally, expenditure at individual events was modest; however the cumulative expenditure and the overall level of contact was high. The available information suggests that companies exert influence over the educational content of events in most cases, and doctors in training are often present at these functions. There is substantial evidence that attendance at company-sponsored events modifies prescribing practices [13]–[15]. The presence of doctors in training and students (in hospital-based sessions) may lead to a process of enculturation whereby they come to regard repeated contact with pharmaceutical companies as a normal and acceptable part of their professional practice. The data reviewed here indicate that, from a company perspective, it is cheap and easy to sponsor meetings in hospitals and health centres, and the return on this “investment” is likely to be high. Equally, it is straightforward for administrators to limit sponsorship of such activities, should they choose to do so. It is difficult to see a role for pharmaceutical companies at hospital grand rounds.

The evidence from this analysis of Australian data suggests that disclosure requirements should not stipulate thresholds—set dollar amounts below which disclosure is not required. Physician-reporting requirements such as those in Vermont and Minnesota in the US, which exempt payments of less than US$100, could obscure the broad cumulative influence of a number of smaller payments [5],[16]. The literature indicates that it is not only the size of the gift that matters—it is the sense of reciprocity that it engenders [17].

The types of activities described here need to be viewed within the broader context of other forms of pharmaceutical industry interaction with doctors, including face-to-face contact with representatives, advertising in medical journals, consultancies, membership of advisory boards, and stock holding [18]–[20]. While lavish gifts and generous travel support have been a focus of attention in the past, these have been progressively discouraged by industry and professional guidelines. It is likely that the frequent, more modest, sponsored educational events will become increasingly important and influential, and the principal form of contact between industry and health professionals.

There are a number of organisations that will benefit from more comprehensive disclosure of these activities. Professional organisations and accreditation bodies will have accurate data on the level and type of contact their members have with pharmaceutical companies. This will enable them to counter the undesirable effects of such relationships through the development of guidelines, or the evolution of practice standards or disciplinary codes. They will benefit from sequential data to determine if practices are changing over time. The public, the media, and consumer groups will have access to reliable data on which to base their judgements about industry-health professional contact and, when appropriate, to lobby for change. Individual health professionals could have access to information on which to judge their own practices against those of their peers. If legislation is thought necessary, governments will have data on which to monitor its impact.

Proposals for Greater Transparency

The Australian reporting standards are deficient in not including details that enable a judgement about the educational value of company sponsored events. We believe that reporting schemes should require the following details: the names of the speakers presenting, whether sponsors played a role in suggestion or selection of speakers or the development of the content of presentations, and the nature of any direct or indirect financial ties between the speakers and the sponsors. This type of information is routinely requested by professional journals; so there are ample precedents and it is particularly relevant when judging the appropriateness of educational events.

We experienced considerable difficulty in accessing the Australian data, which are compiled in portable document format (pdf). As suggested in the US Sunshine Acts it is important that summary reports listing each function are accessible to the public in a searchable, downloadable, and analysable format [5]–[7].

Whether there should be a central register or database that identifies attendees at company-sponsored functions is more controversial. The data could be compiled from the records of names collected by the pharmaceutical companies. Reports could be provided to health professionals, which would enable them to compare their practices with their peers. We are not here advocating public disclosure of this information, but individuals could be asked to provide reports in particular circumstances—for instance when ethics committees are considering the industry ties of an investigator.

In Box 2 we have summarised the main data elements that we think should be included in disclosure programs. What we suggest is consistent with the recent Institute of Medicine (IOM) Report on conflicts of interest [21]. This report recommended that the US Congress create a national program requiring companies and their foundations to publicly report payments to physicians and other prescribers, biomedical researchers and their institutions, but did not suggest specific data elements. Some authors of the report argued that this database should also provide explanatory material about payments received (e.g., for an educational or marketing purpose) and information on all financial ties (e.g., equity ownership, patent rights) in addition to industry payments and gifts [22].

While it may be unrealistic and undesirable to ban contact between pharmaceutical companies and health professionals we should work to make those relationships completely transparent. We welcome further debate on this topic.

Acknowledgments

Thanks to Joanne Knight for her contribution to coding the data.

Author Contributions

ICMJE criteria for authorship read and met: JR RM EW LB DH. Agree with the manuscript's results and conclusions: JR RM EW LB DH. Designed the experiments/the study: RM. Analyzed the data: JR EW DH. Collected data/did experiments for the study: EW. Wrote the first draft of the paper: RM. Contributed to the writing of the paper: JR RM EW LB DH. Developed the data coding scheme, checked all data entries, designed and co-ordinated data analyses, interpreted the data: JR. Conceptualization and interpretation: LB. Helped design the data collection instrument and analysis plan: LB.

References

1. Association of American Medical Colleges (2008) Industry funding of medical education: report of an AAMC task force, June 2008. Available: https://services.aamc.org/Publications/showfile.cfm?file=version114.pdf&prd_id=232&prv_id=281&pdf_id=114 . Accessed 8 May 2009.

2. Greenland P (2009) Time for the medical profession to act. Arch Intern Med 169: 829–831. Find this article online

3. Harris G (2008 October 4) Top psychiatrist didn't report drug maker's pay. New York Times; A1.

4. Rothman DJ, Chimonas S (2008) New developments in managing physician-industry relationships. JAMA 300: 1067–1069. Find this article online

5. Ross JR, Lackner JE, Lurie P, Gross CP, Wolfe S, et al. (2007) Pharmaceutical company payments to physicians. JAMA 297: 1216–1223. Find this article online

6. (2009) Senate Bill S.301. Physician Payments Sunshine Act of 2009. Available: http://thomas.loc.gov/cgi-bin/bdquery/D?d111:3:./temp/~bdhqHM:L&summ2=m&/bss/111search.html . Accessed 13 May 2009.

7. (2008) House of Representatives Bill H.R.5605. Physician Payments Sunshine Act of 2008. Available: http://thomas.loc.gov/cgi-bin/query/D?c110:9:./temp/~c110EAsKeZ . Accessed 13 May 2009.

8. Medicines Australia (2009) Educational Event Reports. Available: http://www.medicinesaustralia.com.au/pages/page136.asp . Accessed 8 May 2009.

9. Australian Competition and Consumer Commission (27 June 2007) Australian competition tribunal affirms ACCC's decision on extra reporting for Medicines Australia Code. Press release number MR 163/07. Available: http://www.accc.gov.au/content/index.phtml/itemId/790845/fromItemId/621589?pageDefinitionItemId=16940 . Accessed 8 May 2009.

10. Medicines Australia (28 March 2008) Medicines Australia sets world-first in transparency. Press release. Available: http://www.medicinesaustralia.com.au/pages/images/MR%20Mar%202803%20MA%20sets%20precedent65.pdf . Accessed 13 May 2009.

11. Medicines Australia (2009) Glossary - educational event report table contents. Available: http://www.medicinesaustralia.com.au/pages/page144.asp . Accessed 8 May 2009.

12. Medicines Australia.Member company reports, and non-member company reports, 1 July–31 December 2007. Member reports: Available: http://www.medicinesaustralia.com.au/pages/page230.asp ; Nonmember reports: Available: http://www.medicinesaustralia.com.au/pages/page500.asp . Accessed 8 May 2009.

13. Wazana A (2000) Physicians and the pharmaceutical industry: is a gift ever just a gift? JAMA 283: 373–380. Find this article online

14. Steinman MA, Harper GM, Chren MM, Landefeld CS, Bero LA (2007) Characteristics and impact of drug detailing for gabapentin. PLoS Med 4: e134. doi:10.1371/journal.pmed.0040134.

15. Hemminki E, Karttunen T, Hovi SL, Karro H (2004) The drug industry and medical practice – the case of menopausal hormone therapy in Estonia. Soc Sci Med 58: 89–97. Find this article online

16. Ross JS, Nazem AG, Lurie P, Lackner JE, Krumholz HM (2008) Updated estimates of pharmaceutical company payments to physicians in Vermont. JAMA 300: 1998–2000. Find this article online

17. Katz D, Caplan AL, Merz JF (2003) All gifts large and small. Am J Bioeth 3: 39–46. Find this article online

18. Gagnon MA, Lexchin J (2008) The cost of pushing pills: A new estimate of pharmaceutical promotion expenditures in the United States. PLoS Med 5: e1. doi:10.1371/journal.pmed.0050001.

19. Norris P, Herxheimer A, Lexchin J, Mansfield P (2005) Drug promotion: what we know, what we have yet to learn. Geneva: World Health Organization. Available: http://www.who.int/entity/medicines/areas/rational_use/drugPromodhai.pdf . Accessed 13 May 2009.

20. Blumenthal D (2004) Doctors and drug companies. N Engl J Med 351: 1885–1890. Find this article online

21. Institute of Medicine (2009) Policies on conflict of interest: Overview and evidence. In: Lo B, Field MJ, editors. Conflict of interest in medical research, education, and practice. Washington (D.C.): The National Academies Press. pp. 51–78.

22. Bero L, Krughoff R, Loewenstein G (2009) Appendix F: Model for broader disclosure. In: Lo B, Field MJ, editors. Conflict of interest in medical research, education, and practice. Washington (D.C.): The National Academies Press. pp. 325–330.

23. Medicines Australia (2008) Code of Conduct Annual Report 2008. Available: http://www.medicinesaustralia.com.au/pages/images/Code-of-Conduct-2008-Annual-Report.pdf . Accessed 8 May 2009.

Pregnancy, not nevirapine cause of liver toxicities in HIV-positive women

Eduard Grebe — Thu, 19 Nov 2009 15:20:02 +0000

Michael Carter writes on aidsmap:

Results of US research “challenge the notion that nevirapine is uniquely associated with hepatotoxicity during pregnancy.” The study did however show that pregnancy itself increased the risk of liver toxicities in women with HIV. The research is published in the November 27th edition of AIDS.

Increased risk of hepatotoxicity in HIV-infected pregnant women receiving antiretroviral therapy independent of nevirapine exposure.

Ouyang DW, Shapiro DE, Lu M, Brogly SB, French AL, Leighty RM, Thompson B, Tuomala RE, Hershow RC.

OBJECTIVE: To estimate whether the association between nevirapine (NVP) and hepatotoxicity differs according to pregnancy status in HIV-infected women. METHODS: The present analysis included HIV-infected pregnant women on antiretroviral therapy (ART) from two multicenter, prospective cohorts - the Women and Infants Transmission Study and the International Maternal Pediatric Adolescent AIDS Clinical Trials protocol P1025 - and HIV-infected nonpregnant women from one multicenter, prospective cohort - the Women's Interagency HIV Study. Using multivariate Cox proportional hazards regression, the interaction between NVP and pregnancy status in terms of hepatotoxicity was investigated. NVP use was dichotomized as use or no use and was further categorized according to ART exposure history. We investigated two outcomes: any liver enzyme elevation (LEE; grade 1-4) and severe LEE (grade 3-4). RESULTS: Data on 2050 HIV-infected women taking ART were included: 1229 (60.0%) pregnant and 821 (40.0%) nonpregnant. Among the pregnant women, 174 (14.2%) developed any LEE and 15 (1.2%) developed severe LEE as compared with 75 (9.1%) and 5 (0.6%), respectively, of the nonpregnant women. In multivariate adjusted models, NVP was not significantly associated with risk of LEE, regardless of pregnancy status; however, pregnancy was associated with an increased risk of any LEE (relative risk 4.7, confidence interval = 3.4-6.5) and severe LEE (relative risk 3.8, confidence interval = 1.3-11.1). The association of pregnancy and LEE was seen, regardless of prior ART and NVP exposure history. CONCLUSION: No significant association between NVP and LEE was observed, regardless of pregnancy status, but pregnancy was significantly associated with increased hepatotoxocity in HIV-infected women.

PMID: 19617813 [PubMed - in process]

Poor provider care leads to poor health-seeking behaviour

Eduard Grebe — Sat, 19 Sep 2009 23:47:12 +0000

What are the causes of AIDS denialism? What are the factors that lead to a loss of public confidence in medical science? Often on aidstruth.org we have focused on debunking the false propaganda of prominent AIDS denialists, but there are other very important causes of people with chronic illnesses choosing to forsake scientifically based medical advice. A crucial one is the often substandard quality of care people receive from their medical practitioners. In the United States, tens of millions of uninsured and under-insured people experience the health system as uncaring and unproviding. In South Africa, where AIDS denialism had its worst effects, a study by Jane Goudge and colleagues at the Centre for Health Policy on the University of Witwatersrand found that "Poor provider-patient interaction led to inadequate understanding of illness, inappropriate treatment action, 'healer shopping', and at times a break down in cooperation, with the patient 'giving up' on the public health system." Healer shopping, or perhaps more appropriately quack shopping, is a consequence of poor health services characterised by disrespectful behaviour from overworked health staff, long waiting lists, queues, and the unavailability of essential medicines and diagnostics. It is here where prominent AIDS denialists and charlatans step into the breach and lead vulnerable people away from proven health interventions. This is yet another excellent reason why decent medical services need to be accessible by middle- and low-income people. Below is the abstract of this study.

Affordability, availability and acceptability barriers to health care for the chronically ill: longitudinal case studies from South Africa.

BMC Health Serv Res. 2009; 9: 75.

Pubmed abstract: http://www.ncbi.nlm.nih.gov/pubmed/19426533

Full free text available here: http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid...

Goudge J, Gilson L, Russell S, Gumede T, Mills A.

Centre for Health Policy, School of Public Health, University of Witwatersrand, Johannesburg, South Africa. jane.goudge@gmail.com

BACKGROUND: There is an increasing burden of chronic illness in low and middle income countries, driven by TB/HIV, as well as non-communicable diseases. Few health systems are organized to meet the needs of chronically ill patients, and patients' perspectives on the difficulties of accessing care need to be better understood, particularly in poor resourced settings, to achieve this end. This paper describes the experience of poor households attempting to access chronic care in a rural area of South Africa.

METHODS: A household survey (n = 1446 individuals) was combined with qualitative longitudinal research that followed 30 case study households over 10 months. Illness narratives and diaries provided descriptive textual data of household interactions with the health system.

RESULTS: In the survey 74% of reported health problems were 'chronic', 48% of which had no treatment action taken in the previous month. Amongst the case study households, of the 34 cases of chronic illness, only 21 (62%) cases had an allopathic diagnosis and only 12 (35%) were receiving regular treatment. Livelihoods exhausted from previous illness and death, low income, and limited social networks, prevented consultation with monthly expenditure for repeated consultations as high as 60% of income. Interrupted drug supplies, insufficient clinical services at the clinic level necessitating referral, and a lack of ambulances further hampered access to care. Poor provider-patient interaction led to inadequate understanding of illness, inappropriate treatment action, 'healer shopping', and at times a break down in cooperation, with the patient 'giving up' on the public health system. However, productive patient-provider interactions not only facilitated appropriate treatment action but enabled patients to justify their need for financial assistance to family and neighbours, and so access care. In addition, patients and their families with understanding of a disease became a community resource drawn on to assist others.

CONCLUSION: In strengthening the public sector it is important not only to improve drug supply chains, ambulance services, referral systems and clinical capacity at public clinics, and to address the financial constraints faced by the socially disadvantaged, but also to think through how providers can engage with patients in a way that strengthens the therapeutic alliance.

Evidence accumulating on benefits of starting HAART earlier

Eduard Grebe — Thu, 20 Aug 2009 15:34:55 +0000

A number of studies showing a benefit to starting antiretroviral therapy earlier have been reported recently. These have resulted in important changes to guidelines including that infants should be treated immediately upon diagnosis and that adults should be treated as soon as their CD4 counts fall below 350 cells/mm3.

Determining the optimal time to start treatment is one of the most important unanswered questions about antiretroviral treatment. A large open-label treatment trial called START has begun and will likely answer this question within the next few years. It is open to HIV-positive volunteers with CD4 counts > 500 cells/mm3. Volunteers will be randomised to either start treatment immediately or defer treatment until their CD4 counts drop to below 350 cells/mm3 or treatment is clinically indicated.

A few of the studies showing the benefits of earlier treatment than guidelines previously recommended are listed below:

Effect of early versus deferred antiretroviral therapy for HIV on survival

N Engl J Med. 2009 Apr 30;360(18):1897-9.

Kitahata MM, Gange SJ, Abraham AG, Merriman B, Saag MS, Justice AC, Hogg RS, Deeks SG, Eron JJ, Brooks JT, Rourke SB, Gill MJ, Bosch RJ, Martin JN, Klein MB, Jacobson LP, Rodriguez B, Sterling TR, Kirk GD, Napravnik S, Rachlis AR, Calzavara LM, Horberg MA, Silverberg MJ, Gebo KA, Goedert JJ, Benson CA, Collier AC, Van Rompaey SE, Crane HM, McKaig RG, Lau B, Freeman AM, Moore RD; NA-ACCORD Investigators.

BACKGROUND: The optimal time for the initiation of antiretroviral therapy for asymptomatic patients with human immunodeficiency virus (HIV) infection is uncertain. METHODS: We conducted two parallel analyses involving a total of 17,517 asymptomatic patients with HIV infection in the United States and Canada who received medical care during the period from 1996 through 2005. None of the patients had undergone previous antiretroviral therapy. In each group, we stratified the patients according to the CD4+ count (351 to 500 cells per cubic millimeter or >500 cells per cubic millimeter) at the initiation of antiretroviral therapy. In each group, we compared the relative risk of death for patients who initiated therapy when the CD4+ count was above each of the two thresholds of interest (early-therapy group) with that of patients who deferred therapy until the CD4+ count fell below these thresholds (deferred-therapy group). RESULTS: In the first analysis, which involved 8362 patients, 2084 (25%) initiated therapy at a CD4+ count of 351 to 500 cells per cubic millimeter, and 6278 (75%) deferred therapy. After adjustment for calendar year, cohort of patients, and demographic and clinical characteristics, among patients in the deferred-therapy group there was an increase in the risk of death of 69%, as compared with that in the early-therapy group (relative risk in the deferred-therapy group, 1.69; 95% confidence interval [CI], 1.26 to 2.26; P<0.001). In the second analysis involving 9155 patients, 2220 (24%) initiated therapy at a CD4+ count of more than 500 cells per cubic millimeter and 6935 (76%) deferred therapy. Among patients in the deferred-therapy group, there was an increase in the risk of death of 94% (relative risk, 1.94; 95% CI, 1.37 to 2.79; P<0.001). CONCLUSIONS: The early initiation of antiretroviral therapy before the CD4+ count fell below two prespecified thresholds significantly improved survival, as compared with deferred therapy. 2009 Massachusetts Medical Society

PMID: 19339714

Timing of initiation of antiretroviral therapy in AIDS-free HIV-1-infected patients: a collaborative analysis of 18 HIV cohort studies

Lancet. 2009 Apr 18;373(9672):1314-6. Free full-text article.

When To Start Consortium, Sterne JA, May M, Costagliola D, de Wolf F, Phillips AN, Harris R, Funk MJ, Geskus RB, Gill J, Dabis F, Miró JM, Justice AC, Ledergerber B, Fätkenheuer G, Hogg RS, Monforte AD, Saag M, Smith C, Staszewski S, Egger M, Cole SR.

BACKGROUND: The CD4 cell count at which combination antiretroviral therapy should be started is a central, unresolved issue in the care of HIV-1-infected patients. In the absence of randomised trials, we examined this question in prospective cohort studies. METHODS: We analysed data from 18 cohort studies of patients with HIV. Antiretroviral-naive patients from 15 of these studies were eligible for inclusion if they had started combination antiretroviral therapy (while AIDS-free, with a CD4 cell count less than 550 cells per microL, and with no history of injecting drug use) on or after Jan 1, 1998. We used data from patients followed up in seven of the cohorts in the era before the introduction of combination therapy (1989-95) to estimate distributions of lead times (from the first CD4 cell count measurement in an upper range to the upper threshold of a lower range) and unseen AIDS and death events (occurring before the upper threshold of a lower CD4 cell count range is reached) in the absence of treatment. These estimations were used to impute completed datasets in which lead times and unseen AIDS and death events were added to data for treated patients in deferred therapy groups. We compared the effect of deferred initiation of combination therapy with immediate initiation on rates of AIDS and death, and on death alone, in adjacent CD4 cell count ranges of width 100 cells per microL. FINDINGS: Data were obtained for 21 247 patients who were followed up during the era before the introduction of combination therapy and 24 444 patients who were followed up from the start of treatment. Deferring combination therapy until a CD4 cell count of 251-350 cells per microL was associated with higher rates of AIDS and death than starting therapy in the range 351-450 cells per microL (hazard ratio [HR] 1.28, 95% CI 1.04-1.57). The adverse effect of deferring treatment increased with decreasing CD4 cell count threshold. Deferred initiation of combination therapy was also associated with higher mortality rates, although effects on mortality were less marked than effects on AIDS and death (HR 1.13, 0.80-1.60, for deferred initiation of treatment at CD4 cell count 251-350 cells per microL compared with initiation at 351-450 cells per microL). INTERPRETATION: Our results suggest that 350 cells per microL should be the minimum threshold for initiation of antiretroviral therapy, and should help to guide physicians and patients in deciding when to start treatment.

PMID: 19361855

Early antiretroviral therapy and mortality among HIV-infected infants

N Engl J Med. 2008 Nov 20;359(21):2233-44.

Violari A, Cotton MF, Gibb DM, Babiker AG, Steyn J, Madhi SA, Jean-Philippe P, McIntyre JA; CHER Study Team.

BACKGROUND: In countries with a high seroprevalence of human immunodeficiency virus type 1 (HIV-1), HIV infection contributes significantly to infant mortality. We investigated antiretroviral-treatment strategies in the Children with HIV Early Antiretroviral Therapy (CHER) trial. METHODS: HIV-infected infants 6 to 12 weeks of age with a CD4 lymphocyte percentage (the CD4 percentage) of 25% or more were randomly assigned to receive antiretroviral therapy (lopinavir-ritonavir, zidovudine, and lamivudine) when the CD4 percentage decreased to less than 20% (or 25% if the child was younger than 1 year) or clinical criteria were met (the deferred antiretroviral-therapy group) or to immediate initiation of limited antiretroviral therapy until 1 year of age or 2 years of age (the early antiretroviral-therapy groups). We report the early outcomes for infants who received deferred antiretroviral therapy as compared with early antiretroviral therapy. RESULTS: At a median age of 7.4 weeks (interquartile range, 6.6 to 8.9) and a CD4 percentage of 35.2% (interquartile range, 29.1 to 41.2), 125 infants were randomly assigned to receive deferred therapy, and 252 infants were randomly assigned to receive early therapy. After a median follow-up of 40 weeks (interquartile range, 24 to 58), antiretroviral therapy was initiated in 66% of infants in the deferred-therapy group. Twenty infants in the deferred-therapy group (16%) died versus 10 infants in the early-therapy groups (4%) (hazard ratio for death, 0.24; 95% confidence interval [CI], 0.11 to 0.51; P<0.001). In 32 infants in the deferred-therapy group (26%) versus 16 infants in the early-therapy groups (6%), disease progressed to Centers for Disease Control and Prevention stage C or severe stage B (hazard ratio for disease progression, 0.25; 95% CI, 0.15 to 0.41; P<0.001). Stavudine was substituted for zidovudine in four infants in the early-therapy groups because of neutropenia in three infants and anemia in one infant; no drugs were permanently discontinued. After a review by the data and safety monitoring board, the deferred-therapy group was modified, and infants in this group were all reassessed for initiation of antiretroviral therapy. CONCLUSIONS: Early HIV diagnosis and early antiretroviral therapy reduced early infant mortality by 76% and HIV progression by 75%. (ClinicalTrials.gov number, NCT00102960.) 2008 Massachusetts Medical Society

PMID: 19020325

Starting Antiretroviral Therapy Earlier Yields Better Clinical Outcomes: Interim Review Leads to Early End of Clinical Trial in Haiti

Monday, June 8, 2009. National Institute of Allergy and Infectious Diseases (NIAID) - Press Release

A clinical trial has demonstrated that HIV-infected adults in a resource-limited setting are more likely to survive if they start antiretroviral therapy (ART) before their immune systems are severely compromised.

On May 28, 2009, an independent data and safety monitoring board (DSMB) met to conduct an interim review of an ongoing clinical study known as CIPRA HT 001, which is being conducted in Haiti. The DSMB found overwhelming evidence that starting ART at CD4+ T cell counts—a measure of immune health—between 200 and 350 cells per cubic millimeter (mm3) improves survival compared with deferring treatment until CD4+ T cells drop below 200 cells/mm3. In light of these results, the DSMB recommended that the trial sponsor—the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health—end the trial immediately, before its scheduled conclusion. NIAID agreed with the DSMB recommendation, and all study participants who have fewer than 350 CD4+ T cells/mm3 will be offered ART.

The study investigators say this new finding has the potential to change the standard of care for HIV infection in dozens of countries around the world where ART is initiated only when CD4+ T cell counts drop below 200 cells/mm3. Like the results of several recent epidemiologic studies in developed countries that examined the optimal time to begin ART, the new finding underscores the importance of identifying people who are HIV-infected earlier in the course of their infection and starting ART earlier.

“The public health community now has evidence from a randomized, controlled clinical trial—the gold standard—that starting ART at CD4+ T cell counts between 200 and 350 cells/mm3 in resource-limited settings yields better health outcomes than deferring treatment until CD4+ T cell counts drop below 200 cells/mm3,” says NIAID Director Anthony S. Fauci, M.D.

“The number of people who meet the medical criteria for receiving ART likely will grow as treatment guidelines are revised as a consequence of this finding, challenging the global community to supply antiretroviral drugs to all who need them,” adds Carl Dieffenbach, Ph.D., director of the NIAID Division of AIDS. “Today, only 30 percent of HIV-infected individuals in low- and middle-income countries who need ART are receiving it.”

The clinical trial CIPRA HT 001 began in 2005. It is funded by NIAID through the Comprehensive International Program of Research on AIDS (CIPRA) and is being carried out by the Haitian Group for the Study of Kaposi’s Sarcoma and Immune Deficiency Disorders (GHESKIO) Centers in Port-au-Prince, Haiti. The principal investigator is Jean William Pape, M.D., the director of the GHESKIO Centers and a professor of medicine at Weill Medical College of Cornell University.

The trial enrolled 816 HIV-infected adults ages 18 and older with early HIV disease and CD4+ T cell counts between 200 and 350 cells/mm3. Half of the participants were assigned at random to begin ART within two weeks of enrollment, and the other half were assigned to defer treatment until their CD4+ T cell counts dropped below 200 cells/mm3 or they were diagnosed with AIDS. This deferred treatment is in keeping with the standard of care in Haiti and the current guidelines of the World Health Organization (WHO). The first-line treatment regimen consisted of the anti-HIV drugs zidovudine, lamivudine and efavirenz.

At the time of the DSMB interim review, six participants in the early treatment group had died, while 23 participants in the standard-of-care group had died—nearly four times as many. The DSMB also found that, among participants who began the study without tuberculosis (TB) infection, 18 people in the early treatment had developed TB, while 36 people—twice as many—in the standard-of-care group had developed TB. These results were statistically significant.

In light of these results, the DSMB recommended that NIAID end the trial immediately and that the study team offer ART to all participants in the standard-of-care group who have fewer than 350 CD4+ T cells/mm3. The DSMB also recommended that the study team continue to follow all participants for another year and make every effort to ensure that participants receiving ART continue their therapy. NIAID concurred with these recommendations.

The study investigators are notifying all participants and have notified institutional review boards and national ethics committees involved with CIPRA HT 001 as well as the Haitian Ministry of Health about the findings of the DSMB. Investigators also have shared the information with WHO, the U.S. President’s Emergency Plan for AIDS Relief, and the Global Fund to Fight AIDS, Tuberculosis and Malaria.

For more information about CIPRA HT 001, see Questions and Answers: The CIPRA HT 001 Clinical Trial.

For more information about HIV/AIDS prevention, treatment and research, go to www.aids.gov.

Precursor to HIV causes disease progression in wild chimpanzees

Eduard Grebe — Thu, 30 Jul 2009 22:35:02 +0000

AIDS denialists have claimed that the lack of disease progression in chimpanzees infected with HIV is evidence that the virus is at worst a passenger in human beings and cannot be the cause of AIDS. This was, for example, implied by the journalist Celia Farber in her AIDS denialist piece published in Harper's in 2006.

In the response to Farber, to which several of the AIDSTruth.org team contributed, we wrote:

It is true that HIV replicates inefficiently in chimpanzees, to a much lower level than it does in humans so it usually does not cause disease. However, there are recorded examples of HIV causing immunodeficiency in these animals.

Many agents which cause disease in man are unable to cause disease in a host of other species because they fail to infect, or infect poorly, or produce a different response. HIV has probably been in the chimpanzee population for a very long time. Therefore it is plausible that natural selection has rendered it less harmful.

There is now new compelling evidence that we understated the extent of Farber's factual error. A team of researchers led by Brandon Keele and Beatrice Hahn have analysed mortality in wild chimpanzees infected with SIVcpz, the immediate precursor of HIV-1. They following 94 wild chimpanzees in Tanzania. They found a 10- to 16-fold higher age-corrected death hazard for SIVcpz-infected chimpanzees compared to uninfected chimpanzees. They also found that SIVcpz-infected females were less likely to give birth and had a higher infant mortality rate than uninfected ones. Furthermore, disease progression was associated with a declining CD4 T cell count and increased viral replication, which is characteristic of HIV infection in humans.

They therefore conclude:

These findings challenge the prevailing view that all natural SIV infections are non-pathogenic and suggest that SIVcpz has a substantial negative impact on the health, reproduction and lifespan of chimpanzees in the wild.

Denialists have claimed that AIDS in humans is caused by poverty, antiretrovirals and recreational drugs such as poppers. These explanations are debunked on the AIDStruth myths page and obviously cannot explain disease progression in SIVcpz-infected chimpanzees. This is further evidence that they are not the cause of AIDS in humans.

Here is the abstract of Keele et al.'s letter to Nature:

Keele, B.F. et al. Increased mortality and AIDS-like immunopathology in wild chimpanzees infected with SIVcpz. Nature 460, 515-519 (2009).

African primates are naturally infected with over 40 different simian immunodeficiency viruses (SIVs), two of which have crossed the species barrier and generated human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2). Unlike the human viruses, however, SIVs do not generally cause acquired immunodeficiency syndrome (AIDS) in their natural hosts. Here we show that SIVcpz, the immediate precursor of HIV-1, is pathogenic in free-ranging chimpanzees. By following 94 members of two habituated chimpanzee communities in Gombe National Park, Tanzania, for over 9 years, we found a 10- to 16-fold higher age-corrected death hazard for SIVcpz-infected (n = 17) compared to uninfected (n = 77) chimpanzees. We also found that SIVcpz-infected females were less likely to give birth and had a higher infant mortality rate than uninfected females. Immunohistochemistry and in situ hybridization of post-mortem spleen and lymph node samples from three infected and two uninfected chimpanzees revealed significant CD4⁺ T-cell depletion in all infected individuals, with evidence of high viral replication and extensive follicular dendritic cell virus trapping in one of them. One female, who died within 3 years of acquiring SIVcpz, had histopathological findings consistent with end-stage AIDS. These results indicate that SIVcpz, like HIV-1, is associated with progressive CD4⁺ T-cell loss, lymphatic tissue destruction and premature death. These findings challenge the prevailing view that all natural SIV infections are non-pathogenic and suggest that SIVcpz has a substantial negative impact on the health, reproduction and lifespan of chimpanzees in the wild.

New study shows AIDS deaths under-recorded in South Africa

Eduard Grebe — Mon, 06 Jul 2009 08:30:25 +0000

Former South African President Thabo Mbeki disputed that there was a large AIDS epidemic in South Africa. (1) This was a cornerstone of his promotion of denialist policies. It was echoed by journalist Rian Malan in articles he wrote in Rolling Stone, the Spectator and Noseweek. (2) Mbeki expressed his scepticism when a state institution, the Medical Research Council, released a report titled Adult Mortality in South Africa. It presented unequivocal evidence that HIV was a growing and major cause of death in the country. (3) Mbeki's health minister, Manto Tshabalala-Msimang, tried to suppress the publication of this report. (4)

Over the last decade, the evidence of the country's large AIDS epidemic has accumulated. It is perhaps most succinctly explained with this graph, which demonstrates the unusual and disturbing changing age-pattern of death among adult women in South Africa from 1997 to 2004 , that can only be explained by the AIDS epidemic:

Source: http://www.tac.org.za/community/node/2182

The graph shows how in 2004 the vast majority of female adult deaths occur in young adults as opposed to older ones (compared with Brazil in 2004 and South Africa in 1997). The same pattern occurs in males, albeit that it is not quite as stark.

One of the arguments raised by Malan is that HIV was ranked quite low as a cause of recorded deaths in Statistics South Africa's mortality data and therefore was not a major cause of death. Malan is wrong: many doctors do not write HIV or AIDS as the cause of death on death notification forms (the source of Stats SA's mortality data). There are probably two reasons for this: (1) the disease is highly stigmatised and doctors do not want to put surviving family members at risk of discrimination, despite the fact that death certificate data is supposed to be confidential, and (2) patients with AIDS often die without finding out their status.

A new study has been published in AIDS that confirms this, i.e. that doctors often do not write HIV, AIDS or even a euphemism for these terms (such as retroviral disease or immunocompromised) on death notification forms of people who have died of AIDS.

Patricia Yudkin and her colleagues examined the medical records of all people 28 days or older who died in two suburbs in Cape Town from 1 June 2003 to 31 May 2004. 683 death notification forms were included in their final analysis. (5) Two doctors independently analysed the medical records to determine if AIDS was the cause of death. In the case of a conflicting diagnosis, a third doctor decided. They identified 129 deaths caused by HIV according to medical records. Yet only 35 (27.1%) were ascribed to AIDS on the death notification form. When the various euphemisms for AIDS were accounted for (known as interpretive coding) only 83 (64.3%) indicated AIDS.

With one exception (a 12% sample of all the mortality data published seven years ago), Stats SA reports since 2001 have classified a death as HIV/AIDS only if explicitly coded as such on the death notification form. They do not use interpretive coding because it would be extremely time-consuming to classify all the country's deaths this way.

Only one death was noted as AIDS on a death notification form but not classified as such by the study doctors, though even in this case the death was suggestive of HIV. The method of classification used by Yudkin et al. would still not have identified deaths of people who died of AIDS before presenting to a health facility or private doctor for diagnosis.

This study provides further evidence against the dogma that there is not a large HIV epidemic in South Africa.

References

1. Cherry M. Mbeki disputes AIDS statistics [Internet]. Nature Medicine. 2001 Nov ;7(11):1170.[cited 2009 Jul 4 ] Available from: http://www.popline.org/docs/1558/175308.html

2. Geffen N. Rian Malan Spreads Confusion about AIDS Statistics [Internet]. 2004 Jan 20;[cited 2009 Jul 5 ] Available from: http://www.tac.org.za/newsletter/2004/ns20_01_2004.htm

3. Dorrington R, Bourne D, Bradshaw D, Laubscher R, Timæus IM. The Impact of HIV/AIDS on Adult Mortality in South Africa [Internet]. 2001 Sep ;[cited 2009 Jul 5 ] Available from: http://www.mrc.ac.za/bod/complete.pdf

4. Cape Argus. Minister demanded 'corrective action' at MRC [Internet]. 2002 Apr 17;[cited 2008 Dec 29 ] Available from: http://www.capeargus.co.za/index.php?fSectionId=3571&fArticleId=ct200204...

5. Yudkin P, Burger E, Bradshaw D, Groenewald P, Ward A, Volmink J. Deaths caused by HIV disease under-reported in South Africa [Internet]. AIDS. 2009 Jun 10;[cited 2009 Jul 5 ] Available from: http://www.ncbi.nlm.nih.gov/pubmed/19521232

Patients returning after interrupting HIV care have a high risk of short-term illness and death

Eduard Grebe — Tue, 30 Jun 2009 23:10:50 +0000

Aidsmap reports:

HIV-positive patients who return to care after being lost to follow-up are five times more likely to die in the short term than patients who remain in HIV care, French investigators report in the online edition of AIDS.

“Increased efforts are needed to reduce loss to follow-up and encourage those patients who no longer attend clinic to return to care,” recommend the authors.

Thanks to effective antiretroviral treatment, the prognosis of many HIV-positive individuals is now near-normal. However, despite the benefits of treatment and care some patients stop attending their HIV clinic.

Read the full article on Aidsmap.

Ndiaye B et al. Characteristics of and outcomes in HIV-infected patients who return to care after loss to follow-up. AIDS 23 (online edition), 2009. doi: 10.1097/QAD.0b013e32832e3469

Abstract

The objective of this study was to evaluate the characteristics of and outcomes in HIV-infected patients who returned to care after loss to follow-up (LTFU) in Northern France, between 1997 and 2006. Among the 1007 patients who were followed, 135 patients (13.4%) were LTFU during the study period. Of these 135, 74 (54.8%) returned to care after LTFU. The median duration of LTFU was 19 months. Upon returning to care, 33 out of 74 patients (44.6%) had CD4 cell counts less than 200/mm3 and/or AIDS. Patients who returned to care after LTFU were five times more likely to die than patients who attended clinic regularly.

Study shows the prognostic value of HIV viral load counts and CD4 counts for predicting AIDS and death

Eduard Grebe — Mon, 22 Jun 2009 13:34:11 +0000

Korenromp EL, Williams BG, Schmid GP, Dye C (2009) Clinical Prognostic Value of RNA Viral Load and CD4 Cell Counts during Untreated HIV-1 Infection—A Quantitative Review. PLoS ONE 4(6): e5950. doi:10.1371/journal.pone.0005950

The purpose of the study was to determine if the current World Health Organisation criteria for commencing HAART are appropriate. The study abstract concludes:

Findings support the current WHO recommendation (used with clinical criteria) to start antiretroviral treatment in low-income settings at CD4 thresholds of 200–350 cells/µL, without pre-treatment RNA monitoring – while not precluding earlier treatment based on clinical, socio-demographic or public health criteria.

Interestingly, the authors found:

Mean relative risks per 10-fold higher RNA were 2.0 (95% confidence interval (CI): 1.8–2.5) for AIDS (12 studies, 17 datapoints) and 2.5 (2.1–3.0) for death (9 studies, 10 datapoints). These prognostic risks did not vary over time after seroconversion, or with duration of follow-up, geographical region, baseline CD4, use of antiretroviral mono-/bi-therapy, or average clinical progression rates.

They also found:

In contrast, relative risks per 100 cells/µL lower CD4 increased with time after seroconversion, for both AIDS (10 studies, 14 datapoints) and death (7 studies, 8 datapoints): from 1.0 at seroconversion to an estimated 3.0 (95% CI 2.6–3.4) by 6 years for AIDS (p<0.0001 for trend), and to 2.8 (1.9–3.7) for death (p<0.0001). In multivariate regression, this pattern was not modified by duration of follow-up, geographical region, baseline CD4, use of antiretroviral mono-/bi-therapy or average progression rates.

In other words, viral load and CD4 count predict death. Coupled with the immense evidence that HAART reduces viral load and increases CD4 counts, these findings are, of course, incompatible with AIDS denialist theories.

NIAID: Starting antiretroviral therapy earlier yields better clinical outcomes

Eduard Grebe — Wed, 10 Jun 2009 14:41:30 +0000

NIH/National Institute of Allergy and Infectious Disease

Interim review leads to early end of clinical trial in Haiti

On May 28, 2009, an independent data and safety monitoring board (DSMB) met to conduct a planned interim review of an ongoing clinical study known as CIPRA HT 001, which is being conducted in Haiti. The DSMB found overwhelming evidence that starting ART at CD4+ T cell counts—a measure of immune health—between 200 and 350 cells per cubic millimeter (mm3) improves survival compared with deferring treatment until CD4+ T cells drop below 200 cells/mm3. In light of these results, the DSMB recommended that the trial sponsor—the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health—end the trial immediately, before its scheduled conclusion. NIAID agreed with the DSMB recommendation, and all study participants who have fewer than 350 CD4+ T cells/mm3 will be offered ART.

"The public health community now has evidence from a randomized, controlled clinical trial—the gold standard—that starting ART at CD4+ T cell counts between 200 and 350 cells/mm3 in resource-limited settings yields better health outcomes than deferring treatment until CD4+ T cell counts drop below 200 cells/mm3," says NIAID Director Anthony S. Fauci, M.D.

"The number of people who meet the medical criteria for receiving ART likely will grow as treatment guidelines are revised as a consequence of this finding, challenging the global community to supply antiretroviral drugs to all who need them," adds Carl Dieffenbach, Ph.D., director of the NIAID Division of AIDS. "Today, only 30 percent of HIV-infected individuals in low- and middle-income countries who need ART are receiving it."

The clinical trial CIPRA HT 001 began in 2005. It is funded by NIAID through the Comprehensive International Program of Research on AIDS (CIPRA) and is being carried out by the Haitian Group for the Study of Kaposi's Sarcoma and Immune Deficiency Disorders (GHESKIO) Centers in Port-au-Prince, Haiti. The principal investigator is Jean William Pape, M.D., the director of the GHESKIO Centers and a professor of medicine at Weill Medical College of Cornell University.

The study investigators are notifying all participants and have notified institutional review boards and national ethics committees involved with CIPRA HT 001 as well as the Haitian Ministry of Health about the findings of the DSMB. Investigators also have shared the information with WHO, the U.S. President's Emergency Plan for AIDS Relief, and the Global Fund to Fight AIDS, Tuberculosis and Malaria.

Questions and Answers: The CIPRA HT 001 Clinical Trial

Researchers publish video of HIV transfer between T-cells

Eduard Grebe — Mon, 30 Mar 2009 07:26:59 +0000

In what is surely a serious blow to AIDS denialists, researchers have published video microscopy of HIV transferring between T-cells:

Quantitative 3D Video Microscopy of HIV Transfer Across T Cell Virological Synapses

Wolfgang Hübner,¹ Gregory P. McNerney,³ Ping Chen,¹ Benjamin M. Dale,¹ Ronald E. Gordon,² Frank Y. S. Chuang,³ Xiao-Dong Li,⁴ David M. Asmuth,⁴ Thomas Huser,³^,4 Benjamin K. Chen¹^* The spread of HIV between immune cells is greatly enhanced bycell-cell adhesions called virological synapses, although theunderlying mechanisms have been unclear. With use of an infectious,fluorescent clone of HIV, we tracked the movement of Gag inlive CD4 T cells and captured the direct translocation of HIVacross the virological synapse. Quantitative, high-speed three-dimensional(3D) video microscopy revealed the rapid formation of micrometer-sized"buttons" containing oligomerized viral Gag protein. Electronmicroscopy showed that these buttons were packed with buddingviral crescents. Viral transfer events were observed to formvirus-laden internal compartments within target cells. Continuoustime-lapse monitoring showed preferential infection throughsynapses. Thus, HIV dissemination may be enhanced by virologicalsynapse-mediated cell adhesion coupled to viral endocytosis.

Science 27 March 2009:
Vol. 323. no. 5922, pp. 1743 - 1747
DOI: 10.1126/science.1167525

Children on HAART do extremely well at South African clinic

AIDSTruth — Thu, 12 Feb 2009 12:10:59 +0000

At the 16^th Conference on Retroviruses and Opportunistic Infections (CROI) Dr Tammy Meyers presented data from a large cohort of children on highly active antiretroviral therapy (HAART) at Harriet Shezi Children's Clinic in Chris Hani Baragwanath Hospital, Soweto, South Africa.(1)⁠ Of 2,102 chidren initiated on HAART over a four year period (April 2004 - March 2008), 1734 (82%) are alive and in the programme. Most of these children started HAART with severely compromised immune systems. Based on studies of untreated children at this stage of HIV disease(2)⁠(3)⁠, it is fair to say that nearly all would have been dead had they not been placed on HAART. By the end of the study, half the children had been on HAART for at least 17 months.

Analysis shows that more than 90% of the cohort had less than 400 copies of HIV per millilitre of blood after 18 months on the programme,¹ indicating that treatment was effective. On average, CD4 percentage rose from 11% to over 25% (in children CD4 percentage, rather than CD4 count is used because it is more stable). HIV-positive children on average weigh less and are shorter than HIV-negative children of the same age. The children in the cohort showed remarkable improvements in both these measures.

132 (6%) children died. Most deaths occurred within the first 90 days of treatment, indicating that many started too late. Meyers made the excellent point that infants should now be treated immediately upon diagnosis. This is based on the findings of the CHER study, published last year, which showed that treating infants treated immediately upon diagnosis (as opposed to deferring treatment until their CD4 percentage met the current SA guidelines for initiating treatment) had much lower mortality.(4)⁠ The factors at baseline that predicted death were being severely underweight, having a high viral load, being on TB treatment and being young. But even among some of these categories children did well. For example, 28.6% of children were on TB treatment, a much greater percentage than the number of deaths.

Both clinical trials and cohorts of children have previously been published showing excellent results on HAART. For example, a widely publicised successful cohort on 94 Haitian children was reported in 2005.(5)⁠ The contribution of the Harriet Shezi study is that this is a very large African cohort in a resource-limited operational setting.

Details

There were 3,553 children in the clinic database. 369 were excluded because they were in the clinic before the start of the cohort period. Another 389 were excluded because they had no follow-up. This left 2,795, of whom 2,216 were initiated on HAART. 91 were excluded from the study because they had no further visits after initiation. 23 were excluded because they were over 15. Of the remaining 2,102 included in the analysis, 1,734 were alive and active at study end. 132 died. 104 transferred and 132 were lost to follow up.

Interestingly of the 579 who did not start HAART (presumably in most cases because they were ineligible according to SA guidelines), 264 are alive and active in the programme. 78 died (double the proportion in the treatment cohort). 189 were lost to follow up (more absolutely than the treatment cohort) and 67 transferred.

At baseline: 51% of the cohort were males. Median viral load was over 100,000 [IQR log viral load: 4.6-5.8]. Median CD4 percentage was 11.5 [IQR: 6.9-16.2]. Weight for age Z-score median was -2.12 [IQR: -3.3 to 1.14]. Height for age Z-score median was -2.6 [IQR: -3.6 to -1.7]. Median age was 4.3 years.

The median follow-up time on HAART was 17.05 months [IQR 5.7-29.2]. The mortality rate within the first 90 days was nearly 15 per 100 child years (CY) and about 2 per 100CY after that (might be slightly inaccurate based on reading off graph). The mortality rate was markedly higher in children under 18 months, over 30 per 100CY within the first 90 days and 5 per 100CY after that. Viral load after 18 months given in the summary is a Kaplan Meier estimate. Based on a graph reading, the median CD4 rose to between 25 and 30%.

An important conclusion by the authors is that a high percentage of children starting HAART are co-treated for TB, warranting investigation of drug interactions.

References

1. Moultrie H, Yotebieng, M, Kuhn L, Meyers T. Mortality and Virological Outcomes of 2105 HIV-infected Children Receiving ART in Soweto, South Africa [Internet]. In: 16th Conference on Retroviruses and Opportunistic Infections. 2009. [cited 2009 Feb 11 ] Available from: http://www.retroconference.org/AbstractSearch/Default.aspx?Conf=18&Abs=35418

2. Little K, Thorne C, Luo C, Bunders M, Ngongo N, McDermott P, Newell M. Disease progression in children with vertically-acquired HIV infection in sub-Saharan Africa: reviewing the need for HIV treatment [Internet]. Curr HIV Res. 2007 Mar ;5(2):139-53.[cited 2009 Feb 11 ] Available from: http://www.ncbi.nlm.nih.gov/pubmed/17346131

3. Cross Continents Collaboration for Kids Analysis and Writing Committee. Markers for predicting mortality in untreated HIV-infected children in resource-limited settings: a meta-analysis [Internet]. AIDS. 2008 Jan 2;22(1):97-105.[cited 2009 Feb 11 ] Available from: http://www.ncbi.nlm.nih.gov/pubmed/18090397

4. Violari A, Cotton MF, Gibb DM, Babiker AG, Steyn J, Madhi SA, Jean-Philippe P, McIntyre JA. Early antiretroviral therapy and mortality among HIV-infected infants [Internet]. N Engl J Med. 2008 Nov 20;359(21):2233-44.[cited 2009 Feb 11 ] Available from: http://www.ncbi.nlm.nih.gov/pubmed/19020325

5. Severe P, Leger P, Charles M, Noel F, Bonhomme G, Bois G, George E, Kenel-Pierre S, Wright PF, Gulick R, Johnson WD, Pape JW, Fitzgerald DW. Antiretroviral Therapy in a Thousand Patients with AIDS in Haiti [Internet]. N Engl J Med. 2005 Dec 1;353(22):2325-2334.[cited 2008 Dec 8 ] Available from: http://www.nejm.org/doi/full/10.1056/NEJMoa051908

1. Based on a Kaplan Meier estimate

CD4 Counts Decline Despite Nutritional Recovery in HIV-Infected Zambian Children With Severe Malnutrition

AIDSTruth — Mon, 26 Jan 2009 17:06:55 +0000

New research in Zambia further undermines the idea that AIDS in Africa is caused by malnutrition. Severe malnutrition did not reduce the CD4 counts of children without HIV. HIV-infected children with severe malnutrition may respond well to nutritional rehabilitation, despite low CD4 counts, but nearly all require early antiretroviral therapy to prevent disease progression.

CD4 Counts Decline Despite Nutritional Recovery in HIV-Infected Zambian Children With Severe Malnutrition.

Hughes SM, Amadi B, Mwiya M, Nkamba H, Mulundu G, Tomkins A, Goldblatt D.

OBJECTIVE. The objective of this study was to establish the contribution that severe malnutrition makes to CD4 lymphopenia in HIV-infected and uninfected children and to determine the changes in CD4 count during nutritional rehabilitation. METHODS. Fifty-six children with severe malnutrition and with and without HIV infection were recruited from a pediatric ward in Lusaka for measurement of CD4 counts on admission, on discharge, and at final nutritional recovery. RESULTS. HIV-uninfected children with severe malnutrition had normal CD4 counts. In contrast, CD4 counts in HIV-infected children with severe malnutrition were reduced, more so in those without edema compared with those with edema. Mean CD4 count of HIV-infected SM children fell despite nutritional recovery so that at the time of full nutritional recovery, >85% of HIV-infected children required antiretroviral therapy. CONCLUSIONS. Severe malnutrition did not reduce the CD4 counts of children without HIV. HIV-infected children with severe malnutrition may respond well to nutritional rehabilitation, despite low CD4 counts, but nearly all require early antiretroviral therapy to prevent disease progression.

PMID: 19124582 [PubMed - as supplied by publisher]

Ethics of science communication on the web

AIDSTruth — Thu, 11 Dec 2008 20:22:54 +0000

The internet is a powerful medium for information dissemination. But since it is also unregulated, much disinformation, including AIDS denialism is spread on the web. Maxine Clarke's recent article on the ethics of science publishing on the web is therefore highly topical. It is included in a special theme section on the ethics of science journalism being built by the journal Ethics in Science and Environmental Politics.

Clarke, M. Ethics of science communication on the web.

ABSTRACT: Scientists have evolved a unit of communication to describe their new results and findings: the peer-reviewed scientific paper. The internet is full of erroneous and even dangerous information that is difficult for people without a scientific education or training to interpret in context, particularly given the uncertainties inherent in the scientific process. Those interpreting science for the public, whether journalists, educators or other communicators, should use peer review as a benchmark.

KEY WORDS: Publishing · Science · Peer review · Internet · Research

Download the paper.